The research proposed in this application is directed at developing novel ceramic scaffolds that are bioresorbable, bioactive, osteoconductive and exhibit high strength. These goals will be achieved through stepwise engineering of the ceramic microstructure, scaffold architecture, micro and nanotopography and surface chemistry. The rationale is that there is currently no synthetic scaffold material that is bioactive, resorbable and exhibits biologically compatible compressive strength. We will first investigate the crystallization kinetics and mechanical properties of sintered niobium- doped fluorapatite (FAp) ceramics with the aim of developing a highly crystalline ceramic with nanosized FAp crystals (Aim 1). We will select the best composition with niobium additions that will induce phase separation, lead to the crystallization of nanosized crystals and high crystallinity. We will then prepare FAp ceramic scaffolds using a carefully engineered approach that combines a pre-coating step, a glazing step and a chemical etching step (Aim 2). We postulate that optimization of the scaffold architecture will lead to superior mechanical properties and that the chemical etching step will promote a complex three-dimensional surface micro and nanotopography later stimulating contact osteogenesis. The effect of ion-exchange on surface chemistry, solubility and bioactivity of the scaffolds will be tested in Aim 3. The overall rationale is that strontium substitution in the apatite structure will increase solubility and bioactivity. Finally, the resorption and bone regeneration ability of the scaffolds will be tested in vivo using a rat calvarial critical defect model and a combination of state of the art in vivo micro-computed tomography and histopathology (Aim 4). The hypotheses tested are that the surface chemistry and topography of the scaffolds will enhance bone regeneration and that the resorption rate will be compatible with the rate of bone regeneration.